350 Discussion 



like what Prof. Lynen has described, where medium is continually 

 dripped in and bacteria grow under steady conditions for many days. 

 Many experiments have been done to show that the organism that 

 grows faster wins out in a short time. 



Siekevitz : In mammalian organs, as has been found by many people, 

 the turnover of the RNA is not necessary for protein synthesis. Also, 

 the RNA in the nucleoprotein particles that I mentioned earlier turns 

 over very slowly, if at all, whereas their determinable protein does so 

 very rapidly. 



Coxon : Is it justifiable to deduce from what Dr. Magasanik said, that 

 the number of potential inducers is limited by the pre-existing enzyme- 

 forming systems in the cell? Presumably there is only a limited class of 

 compounds that could act as inducers if there has to be a pre-existing 

 enzyme-forming system which, in turn, is repressed in the process of 

 induction. 



Magasanik: Yes. It is now thought that the inducer acts on a pre- 

 existing enzyme-forming system. This view is relatively new. Earlier, 

 it was thought that the inducer itself became part of the enzyme-forming 

 system. However, it is known that the formation of each inducible 

 enzyme is genetically controlled ; unless the gene is present, the inducer 

 is incapable of effecting the formation of the enzyme. The gene is 

 thought to have the information which determines the amino acid 

 sequence of the enzyme protein, and to transmit this information to the 

 enzyme-forming system. What additional information, essential for 

 the construction of the enzyme-forming system, could the inducer 

 provide? I think the answer is: none. It is therefore tempting to 

 speculate that the enzyme-forming system is formed independently of 

 the presence or absence of the inducer, but that the inducer acts on the 

 enzyme-forming system, presumably by competing with a specific 

 repressor. According to this hypothesis, the cell will contain at all 

 times all the enzyme-forming systems it is capable of producing, but the 

 rate at which each of these systems turns out the appropriate enzyme 

 will depend on the intracellular levels of the corresponding inducers and 

 repressors, and these, in turn, will depend on the composition of the 

 growth medium. 



Lehninger: Dr. Magasanik, Monod found that he could induce an 

 enzyme with a substance which does not necessarily act as a substrate. 

 Can you repress enzyme formation with something that is not technic- 

 ally a product of the enzyme that you are repressing? 



Magasanik : Yes. Mr. A. P. Levin in our laboratory had found (unpub- 

 lished data) that the guanine analogue, azaguanine, represses the forma- 

 tion of inosinicase and of inosinic acid dehydrogenase in the same way as 

 guanine. This effect of azaguanine is distinct from any general inhibitory 

 effect of this compound on protein synthesis, since the formation of 

 other enzymes, e.g. glycerol dehydrogenase, is not inhibited under these 

 conditions. I should add that analogues of amino acids may mimic the 

 inhibitory action of the corresponding amino acid on an early step of 

 their biosynthetic pathway. This would explain why an organism cannot 

 overcome the growth-inhibitory effect of such an analogue by producing 



